3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors.
10.1016/j.apsb.2017.04.009
- Author:
Hasnah OSMAN
1
;
Nor Hashima IDRIS
1
;
Ezatul Ezleen KAMARULZAMAN
2
;
Habibah A WAHAB
2
;
Mohd Zaheen HASSAN
1
Author Information
1. School of Chemical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800 USM, Malaysia.
2. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800 USM, Malaysia.
- Publication Type:Journal Article
- Keywords:
Dengue virus;
NS2B/NS3 protease;
Piperidone;
Protease inhibitors;
α,β-Unsaturated ketone
- From:
Acta Pharmaceutica Sinica B
2017;7(4):479-484
- CountryChina
- Language:English
-
Abstract:
Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues-were synthesized and screenedagainst DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through anDENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (and) emerged as promising lead molecules for novel protease inhibitors with an ICof 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having ICof 57.28 µmol/L.
